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New Advances in Interventional Pulmonology

Targeted Options for Lung Cancer Treatment 2019

Finbar Foley, MD, MPH

Instructor

Section of Pulmonary, Critical Care, and Sleep Medicine

Yale University School of Medicine

May 2019

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Conflicts of Interest:

• Nothing to disclose

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Objectives:

• Explore current and future directions for interventional pulmonology lung cancer diagnostics and treatments

– Evolution of peripheral nodule biopsies

• Review 2019 guidelines for malignant pleural effusions (if time permits)

– Focus on advice relevant to general providers

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Interventional Pulmonology in Lung Cancer Diagnosis

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Solitary Nodule and Lung Cancer Screening

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Location: peripheral vs central?

NELSON trial : 15,822 participants

• 62% in the periphery (outer 1/3rd)

• RUL predominance

Horeweg AJRCCM 2013

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Interventional Pulmonology – balance risk/benefit

• A CT-guided approach is often more accurate (95%)

• A surgical approach is often definitive and possibly curative

• The bronchoscopist’s goal should be to approach the yield of these two techniques while providing the lowest morbidity

PNEUMOTHORAX

MORBIDITY and COST

Minimal pneumothoraxMinimal morbidity

Least cost

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Transthoracic biopsy

Diagnostic yield : 90-95%

Complications :

Pneumothorax 10-17%: ~ 7% require chest tube

Hemorrhage 1%

No significant difference in yield between lesions < 2cm and > 2cm

De Margerie-Mellon Diag & Interv Imaging 2016Wiener Annals of Int Med 2011Manhire BTS guidelines Thorax 2003

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Benefits of Bronchoscopic Approach

• Lower risk of pneumothorax (~1%)

• Opportunity to stage simultaneously (EBUS lymph node sampling)

• Potential for direct lesion visualization

• Better able to assess non-malignant causes for nodules (e.g. infection)

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CentralTumors*

PeripheralTumors

Overall Yield w/ Combined Techniques

88% 78%

Biopsy 74% (Endobronchialtumor)

57% (TBBx)

Washing 48% 43%

Brushing 59% 54%

Rivera CHEST 2013

For peripheral tumors – yield increased with number of TBBx samples1 sample – 45%6 samples – 70%

Conventional Bronchoscopic Methods: Location matters

* Endobronchial, submucosal tumors and peribronchial with extrinsic compression

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Conventional Bronchoscopic Methods: Size matters• Nodule < 3cm

• Mass > 3cm in largest diameter

• “Conventional” Bronchoscopy

– BAL/EBBx/TBBx without EBUS/EMN

Size Prevalence of Malignancy

Yield ofConventional TBBx

< 0.5cm 0-1%~ 34%

0.5-1.0 cm 6-28%

1-2 cm 33-64%

> 2 cm 64% - 82%Up to 63%

> 3 cm 93-97%

Ha et al Cleveland MedEd 2014Ost Fishman’s Pulm Diseases 5 e

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Advanced Techniques – Getting closer, seeing more

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Ultrathin bronchoscopes

• Limitations

– Smaller working channel

• Less suction

• Smaller instruments

– Less rigidity

– Poorer image quality

Panchabhai and Mehta Ann ATS 2015

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Radial Probe EBUS (RP-EBUS; pEBUS)

• Confirms location of nodule in real time

– Does not allow “real-time” biopsies

• For detection of lung cancer in peripheral lesions :

– Pooled sensitivity 73%, specificity 100%

– Diagnostic yield: 56% < 2cm, 78% > 2cm

Rivera CHEST 2013

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Guide Sheath + Radial EBUS

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Radial EBUS in lesion

Even when lesion is reached, the biopsy is not in “real time”

Diagnostic yield (496 pts):

Concentric view (within) - 84%Eccentric view (adjacent) – 48%

Chen Annals ATS 2014Evison JTO 2014

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Left Lower Lobe Nodule – How to get there?

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Virtual bronchoscopy

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Electromagnetic Navigation Bronchoscopy

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Meta-Analysis of Navigational Bronchoscopy

• 2015 : 17 studies

Pooled sensitivity and specificity : 82% and 100%

Diagnostic odds ratio : 97%

• 2014 : 15 studies , 1033 lung nodules

Diagnostic accuracy overall : 73.9%

Increased yield size

Radial EBUS use

“bronchus sign”

Decreased yield lower lobe location

Overall pneumothorax rate: Similar to conventional bronchoscopy

Zhang JTD 2015Gex Respiration 2014

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Overall Diagnostic Yield with New Technology

• Guide sheath 73.2%

• Virtual bronchoscopy 72%

• Radial EBUS 71.1%

• EMN / ENB 67%

Wang Memoli, J, Nietert, P and

Silvestri. Chest 2011.

Meta-analysis of 39 studies with over 3000 patients

Pneumothorax rate: 1.6%Chest tube required: 0.6%

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So What’s New?

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Robotic Bronchoscopy

• 3.2mm outer diameter scope, 1.2mm working channel

• 180 degree flex in any direction

• Permits direct continuous visualization of lesions throughout the biopsy procedure

• Deeper reach

– 9th vs 6th generation airways

• 17 patient feasibility study:

– “bronchus sign” lesions

– Direct visualization of biopsy in 14/15

Jackson, Barbara, JaneJackson, Barbara, Jane

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A cc#: E106601525A cc#: E106601525

DO B: 5/4/1941DO B: 5/4/1941

F/76 YEA RF/76 YEA R

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Tech: C RTech: C R

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HELIC A L MO DE /9:57:21 A MHELIC A L MO DE /9:57:21 A M

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500ms / mA : 180500ms / mA : 180

KV p: 120 ---KV p: 120 ---

T ilt: 0T ilt: 0

FFSFFS

Page: 123 of 551Page: 123 of 551

IM: 123 SE: 3 IM: 123 SE: 3

C ompressed 8:1C ompressed 8:1

DFO V :36x36cmDFO V :36x36cm

SN: -81SN: -81

THK: 0 .63THK: 0 .63

NI: 0NI: 0

RR LL

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Rojas-Solano et al. BIP 2018

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Potential?

• Higher diagnostic yield, approaching that of CT-guided trans-thoracic needle biopsy, with lower rate of complications

• Benefits of bronchoscopy remain – simultaneous diagnosis and staging procedure

• Potential for therapeutic intervention –

same-day diagnosis and treatment

– Radiofrequency ablation

– Microwave ablation

– Photodynamic therapy

– Brachytherapy

– Vapor ablation

– Cryoablation

– Direct injection of chemotherapy

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Take Home Points

• As lung cancer screening increases, the need for evaluation of small peripheral lung nodules will rise

• For non-surgical patients, CT-guided needle biopsy has superior diagnostic efficacy but higher risk

• Bronchoscopy can provide simultaneous diagnosis, staging, and possibly therapy in future

• Advances in bronchoscopy permit more accurate tissue acquisition from distal lesions, while maintaining safety profile

• Robotic bronchoscopy is the newest modality

– Greater peripheral reach

– Direct visualization of lesions

– May use other modalities to enhance accuracy (navigation, radial EBUS)

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Malignant Pleural Effusions (MPE)

• 2018 – Evidence-based guidelines focusing on management of MPE

– Management of asymptomatic and symptomatic MPE

– Use of pleurodesis vs indwelling (tunneled) pleural catheters

– Management of catheter-associated infection

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Asymptomatic MPE – No need to drain

• Porcel et al 2015: Retrospective study of 556 patients with newly diagnosed lung cancer

– 40% developed pleural effusion

– ½ of these (112 cases, 20% of total) were too small for sampling or intervention

– None of these 122 cases went on to require drainage (follow-up 10 +/-11 months [SD])

• Tremblay et al 2007: Retrospective review of 113 new lung cancer patients

– 34 had pleural effusion, 14 were asymptomatic

– 13/14 followed for median 98 days, none needed intervention

In patients with known or suspected MPE who are asymptomatic, we suggested therapeutic pleural interventions not be performed

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Will patient get better? – Try large-volume thoracentesis

• A patient’s symptoms may not be due to the effusion

– Differential includes pre-existing lung disease, tumor impact, PE, pericardial effusion

– Assess with thoracentesis prior to definitive procedures

– May learn speed of re-accumulation – up to 60% of patients will require repeat within 9 days of initial drainage1

• It is sometimes unclear whether the lung can expand after drainage

– “nonexpandable lung” occurs in 30% of patients with MPEs, and may be a contraindication for pleurodesis2

1Ost et al. Chest 20182Bhatnagar et al. Eur Respir Rev 2016

In patients with symptomatic MPE, if it is uncertain whether the patient’s symptoms are related to the effusion and/or if the lung is expandable, we suggest a large-volume thoracentesis

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Non-expandable lung

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Indwelling Pleural Catheter (IPC) associated infection

• Aggregated data from 3 RCTs1 show IPC-related rates of:

– Cellulitis = 7.3%

– Pleural space infection = 4.6%

• 6 observational studies and 1 nested case series:

– 41/57 patients (72%) managed without removing the IPC

– No data to suggest superiority/inferiority of catheter continuation vs removal

1 Feller-Kopman et al. AJRRCM 2018.

• The problem for which the catheter was placed (MPE) still remains• Initial treatment of pleural infection is…chest tube placement and drainage. • Pleurodesis may result after infection!

In patients with IPC-associated infection, treating through the infection without catheter removal is usually adequate.

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Take Home Points for MPE

• If there is no diagnostic question and the MPE is asymptomatic, drainage is not required

• To determine whether the MPE is symptomatic or whether the lung is re-expandable, perform large-volume thoracentesis first

• If fluid rapidly re-accumulates and symptoms re-develop, definitive intervention is advised

• IPC and chemical pleurodesis are both considerations

– IPC advisable if lung is not re-expanding

• If there is an IPC-associated infection, try to treat through first

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References

Porcel JM, Gasol A, Bielsa S, Civit C, Light RW, Salud A. Clinical features and survival of lung cancer patients with pleural effusions. Respirology. 2015 May;20(4):654-9.

Tremblay A, Robbins S, Berthiamue L, Michaud G. Natural History of Asymptomatic Pleural Effusions in Lung Cancer Patients. Journal of Bronchology. 14(2):98-100, APR 2007.

Ost DE, Niu J, Zhao H, Grosu HB, Giordano SH. Quality Gaps and Comparative. Effectiveness of Management Strategies for Recurrent Malignant Pleural Effusions. Chest. 2018 Feb;153(2):438-452.

Bhatnagar R, Corcoran JP, Maldonado F, Feller-Kopman D, Janssen J, Astoul P, et al. Advanced medical interventions in pleural disease. Eur Respir Rev 2016;25:199–213

Feller-Kopman DJ, Reddy CB, DeCamp MM, Diekemper RL, Gould MK, Henry T, Iyer NP, Lee YCG, Lewis SZ, Maskell NA, Rahman NM, Sterman DH, Wahidi MM, Balekian AA. Management of Malignant Pleural Effusions. An Official ATS/STS/STR Clinical Practice Guideline. Am J Respir Crit Care Med. 2018 Oct 1;198(7):839-849.

Dresler CM, Olak J, Herndon JE 2nd, Richards WG, Scalzetti E, Fleishman SB, Kernstine KH, Demmy T, Jablons DM, KohmanL, Daniel TM, Haasler GB, Sugarbaker DJ; Cooperative Groups Cancer and Leukemia Group B; Eastern Cooperative Oncology Group; North Central Cooperative Oncology Group; Radiation Therapy Oncology Group. Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion. Chest. 2005 Mar;127(3):909-15.

Fysh ETH, Waterer GW, Kendall PA, Bremner PR, Dina S, Geelhoed E, et al. Indwelling pleural catheters reduce inpatient days over pleurodesis for malignant pleural effusion. Chest 2012;142:394–400

Rojas-Solano JR, Ugalde-Gamboa L, Machuzak M. Robotic Bronchoscopy for Diagnosis of Suspected Lung Cancer: A Feasibility Study. J Bronchology Interv Pulmonol. 2018 Jul;25(3):168-175.